Despite the improved survival with antiretroviral therapy (ART), HIV-infected patients still remain at higher risk for chronic comorbidities, including cardiovascular disease (HIV-CVD). Elevated circulating levels of interleukin-6 (IL-6), hsCRP, and D-dimer are associated with increased risks of HIV-CVD. In addition, endothelial dysfunction also appears to be common in ART-treated, HIV-infected patients. However, ART only partially lowers these inflammatory and coagulation biomarkers and only partially improves endothelial function as measured by flow-mediated dilation (FMD) of the brachial artery. One potential explanation for the continued heightened risk of HIV-CVD despite ART that has thus far been completely ignored is depression. Because depressive disorders are found in 20-40% of HIV-infected patients receiving ART, it stands to reason that this common comorbidity may contribute to the persistently elevated risk of CVD in HIV. The central objective of this application is to determine the relationships between depressive disorders and its treatments with systemic inflammation/coagulation and endothelial function in HIV-infected persons. We will address this objective with the following Specific Aims: Specific Aim #1: To determine the associations of depression and exposure to depression treatment with systemic inflammation and altered coagulation in HIV. We will conduct an observational analysis of the large (N=1525) Veterans Aging Cohort Study (VACS) Biomarker Cohort which also includes Patient Health Questionnaire (PHQ)-9 scores, extensive pharmaceutical prescription data, and diagnostic codes for depression and psychotherapy; Specific Aim #2: To determine the effects of cognitive behavioral treatment on systemic inflammation, altered coagulation, and endothelial dysfunction in HIV-infected adults with depression. We will address this aim by conducting a pilot, randomized, 24-week trial using the Beating the Blues cognitive behavioral treatment program in 110 ART-treated patients at Indiana University with suppressed HIV-1 RNA levels and with PHQ-9 defined major depression. Our multidisciplinary research team has the required expertise and resources to successfully address these Aims. The results of these studies will determine the relationships between depression, depression treatment, inflammation/coagulation, and endothelial function in HIV-infected patients by leveraging an existing HIV-CVD cohort and by performing a novel, interventional, pilot trial. As such, this application meets the stated objectives of RFA HL-14-023 and will provide the rationale for future interventional trials to reduce HIV-CVD events by treating depression. This line of research may provide HIV clinicians with novel and easily implementable tools to prevent CVD morbidity and mortality in their patients and will advance the field of HIV- CVD research.